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New study to show how our body clock controls disease

New treatments for inflammatory lung diseases and a host
of other conditions could be developed following a study into the
impact of circadian rhythms - or body clock.

In a partnership between The University of Manchester, the NIHR
Manchester Biomedical Research Centre and GlaxoSmithKline (GSK), a
team of scientists will investigate how our biological clock
controls inflammation in lung diseases such as Chronic Obstructive
Pulmonary Disease (COPD). It is hoped that this project, worth more
than £500,000, will lead to the development of new drugs which will
target how the internal body clock regulates the severity of
inflammation.

The Manchester team is headed by Professors Andrew Loudon, David
Ray and Kath Else, and they will work closely with colleagues in
the Discovery Biology group at GSK. Inflammatory diseases of the
lung are a major cause of mortality world-wide. In the case of
COPD, the progression of this inflammatory disease is irreversible
once commenced. In the UK 27,478 people died as a result of COPD in
2004. Other diseases with an inflammatory aspect include asthma,
which is a predisposition to chronic inflammation of the lungs in
which the airways are reversibly narrowed. This disease affects 7%
of people in the US, 6.5% in the UK and 300 million people
worldwide, and causes 4,000 deaths a year in the US.

In order to develop the drugs, the team will first study the
mechanisms whereby the circadian clock controls the magnitude of
the local inflammatory response; that is, the genes and pathways
that connect the clock to the cells responsible for the immune
response in the lungs. Professor Loudon, of the Faculty of Life
Sciences, explains: "Many inflammatory diseases are highly rhythmic
in presentation and often worse at night."

"We believe there is also a strong rhythmic control. It has long
been speculated that asthma and other inflammatory conditions have
an underlying clock mechanism controlling the severity of the
disease. These clocks are all over the body, including in cells
responsible for the immune response in the lung. In addition the
way we metabolise drugs is highly rhythmic.

"Our aim is to gain a sufficient understanding of this process
so we can target key parts with specific new drugs. "We are working
with GSK not only to develop new drugs to alleviate symptoms but
also reveal optimal timing of therapy, known as chronotherapy. This
is a new and exciting area of research. It is being taken very
seriously in France, for example, where researchers have for some
time been studying the importance of timing of chemotherapy in
cancer."

He adds: "After a decade of research into the area you don't
have to explain to anyone what the circadian clock is these days,
which is a very good thing. But in the last three years we have
gone further, developing very strong links between the basic
science and its clinical application. "We have detailed insight
into how the molecular cogs of the clock work, drive cells and
physiology. We have been looking at it organ by organ, cell by
cell, unraveling how the clock drives the biology of the organism.
Many diseases are rhythmic, so it's no surprise that when the
circadian rhythm is disrupted it is associated with altered
physiology. "This study is just one at the beginning of an exciting
new phase in circadian rhythm research."